# Final Report



# Analysis of Laboratory Capacity

to Support U.S. EPA Chemical

Testing Program Initiatives

Prepared by:

Economics, Policy, and Analysis Branch (7406M)

Office of Pollution Prevention and Toxics

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue NW

Washington, DC 20460

August 30, 2004

# CONTRIBUTORS

The EPA analyst responsible for this report was Lynne Blake-Hedges. Analytical and draft

preparation support was provided by Eastern Research Group, Inc. under subcontract to Abt

Associates Inc. under EPA Contract No. 68-W-02-077.

# TABLE OF CONTENTS (Continued)

Page

ii TABLE OF CONTENTS

Page

1.0 I NTRODUCTION 

# .........................................................................................................1

2.0 D EMAND FOR 

# C HEMICAL 

# T ESTING 

# S ERVICES 

# ............................................................2

2.1 HPV Testing in the United States ................................................................2

2.2 HPV Testing in the European Union ...........................................................3

2.3 OECD/ICCA HPV Testing Program ...........................................................4

2.4 Comparison of U.S. and EU HPV Chemical Testing Programs..............................5

2.5 Impact of the HPV Challenge and REACH on Chemical Testing Demand8

2.6 U.S. Testing for Endocrine Disruption Potential...................................................11

3.0 S UPPLY OF 

# C HEMICAL 

# T ESTING 

# S ERVICES 

# ..............................................................17

3.1 Contract Research Organizations...............................................................17

3.2 Captive In-House Testing Labs .................................................................20

3.3 Other Sources of Testing Capacity ............................................................21

4.0 C URRENT 

# I NDUSTRY 

# I SSUES 

# ....................................................................................21

4.1 Issues Affecting Demand...........................................................................21

4.2 Issues Affecting Supply .............................................................................23

5.0 C ONCLUSIONS 

# .........................................................................................................28

6.0 R EFERENCES 

# ...........................................................................................................30

# 1 1 

# .0 I NTRODUCTION



# Under the authority of the Toxic Substances Control Act (TSCA), the U.S. Environmental

Protection Agency (EPA) is authorized to request from industry certain data on the human health

and ecological effects of commercially produced chem icals, if the Agency determines such test

data is necessary to assist it in assessing the risks from such chemicals. In addition to such

regulatory-driven activities, industry has agreed to collect and submit certain types of chemical

testing data to EPA on a voluntary basis.

In its planning and decisionmaking with resp ect to both regulatory and voluntary chemical

testing initiatives, EPA wishes to be cognizant of the effects of such programs on industry. One

question that has generated significant interest is whether sufficient laboratory capacity is

available to satisfy the demand for chemical testing generated by such programs. 1



# The purpose of this document is to improve EPA’s understanding of the capacity of the chemical

testing industry to respond to current and future testing initiatives. The report summarizes

information on the current and potential future capacity in the industry to perform certain kinds

of chemical tests in the United States, as well as overseas. Because the testing industry operates

internationally, the report focuses not just on U.S. testing initiatives, but those elsewhere that

also affect the global chemical industry, in pa rticular the proposed expansion to the testing

program in the European Union (see Section 2.2).

In this report, the term “chemical testing industry” applies broadly to any organization that has

the capability to use standard laboratory methods to determine the effects that a particular

chemical may have on humans or the environment. These may include contract research

organizations (CROs), whose primary line of busin ess is analytical testing; in-house testing

laboratories maintained by chemical companies or others (who may also do work for hire); as

1 

# A second and related question is whether such capacity is available at a reasonable price. This question,

however, was not explicitly addressed in this report.

# 2 well as laboratories maintained and operated by academic or other institutions. The primary

focus in this report is on CROs, who are likely to undertake the majority of the testing covered

by this report, although Section 3 (supply of testing services) contains a discussion of captive, inhouse labs as well.

This report was prepared using public information compiled for EPA about the chemical testing

industry, discussions with EPA and other experts familiar with the industry, and information

collected first hand from laboratories exhibiting at a major trade show in the spring of 2004.

2 

# .0 D EMAND FOR 

# C HEMICAL 

# T ESTING 

# S ERVICES



# Laboratories and industry observers contacted during the preparation of this report agreed that

the primary driver for the chemical testing industry, presently at least, is the demand for testing

in the biotechnology and pharmaceutical areas. Contracts with biotech and pharmaceutical firms

to conduct product testing currently account for a majority of CRO and in-house testing activity,

and such contracts were deemed most critical to the economic success or failure of a laboratory

(Piccirillo 2003). As a general statement, therefore, the demand for testing generated by EPAmandated (i.e., TSCA) programs, as well as voluntary EPA testing programs, does not dominate

the industry.

It is important to note that activity levels in all testing areas can change, and some labs may be

more dependent on some programs than other. To help understand trends in the marketplace, the

sections below review several major chemical testing programs underway in the U.S., the EU,

and other countries.

2.1 HPV Testing in the United States

In the U.S., one of the primary EPA testing initiatives is the “High Production Volume (HPV)

Challenge” chemical testing program. Under the HPV Challenge, EPA has invited industry to

# 3 voluntarily sponsor the collection of a basic set of test data for the 2,089 chemicals produced or

imported into the U.S. at volumes equal to or in excess of one million pounds. The HPV

Challenge was initiated in response to findings that basic hazard data was unavailable for a

substantial number of HPV chemicals.

Under the program, initiated in 1998, any needed testing should be completed by 2004 and all

data will be made available to the public by 2005 (U.S. EPA 2000). Individual chemicals that

remain unsponsored may be evaluated by EPA as candidates for test rules under Section 4 of

TSCA.

The HPV Challenge uses a set of 15 testing endpoints defined by OECD’s “Screening

Information Data Set” (SIDS). As conceived by the OECD, the “SIDS battery” of tests can be

used by governments to conduct an initial assessment of the hazards and risks posed by HPV

chemical substances, and prioritize HPV chemicals to identify those in need of more in-depth

testing and assessment. More information on the SIDS testing protocols is presented below in

Section 2.4.

2.2 HPV Testing in the European Union

The European Union (EU) operates a testing program for both new chemicals and existing

chemicals produced at high volume, defined in the EU as 1,000 metric tons or greater (2.2

million pounds) (European Chemicals Bureau 2004; Safepharm Laboratories 2003). Currently, it

maintains dossiers on approximately 10,400 existing chemicals (European Chemicals Bureau

2004).

The EU’s proposed Registration, Evaluation and Authorisation of Chemicals (REACH) program

would substantially expand the provisions of the existing chemicals program (Liikanen and

Wallstöm 2003; Miller 2003; Synthetic Organic Chemical Manufacturers Association 2003;

Squire & Sanders 2003). Under current draft guidelines, substances produced or imported in

# 4 annual quantities of 1,000 metric tons (2.2 million pounds) or more would need to be tested

within three years; substances produced or imported at annual quantities of 100 to 1,000 metric

tons (220,000 to 2.2 million pounds) would need to be tested within six years; and substances

produced or imported at annual quantities of 1 to 100 tons (2,200 to 220,000 pounds) would need

to be tested within 11 years. Because it extends coverage to lower volume chemicals, the

REACH proposal encompasses far more chemicals than the U.S. HPV program—an estimated

20,000 chemicals compared with the 2,089 HPV chemicals in the U.S.

Table 1. Proposed EU Chemical Testing Program (REACH)

Threshold volume

Metric tons* Pounds Estimated Number of

Chemicals Time Frame to

Complete Testing

1,000 or greater 2.2 million or greater 1,799

+ 1,061 intermediates within 3 years

between 100 and 1,000 between 220,000 and 2.2

million 1,645 within 6 years

between 10 and 100 between 22,000 and

220,000 3,466

between 1 and 10 between 2.2 and 22,000 11,711 within 11 years

Total chemicals covered 19,682

--

*Metric tons manufactured or imported to the EU on an annual basis.

Source: Risk & Policy Analysts 2003.



# 2.3 OECD/ICCA HPV Testing Program

In 1998, the International Council of Chemical Associations (ICCA), representing the global

chemistry industry, announced an effort to work with OECD to develop test data for 1,000

priority OECD HPV chemicals (ICCA 2002). The program has a goal of completing SIDS

testing and initial hazard assessments on these chemicals by the end of 2004. This program is

based on a broad international collaboration of chemical manufacturers. Under the HPV

Challenge, EPA is recognizing commitments made to complete testing under the ICCA initiative

# 5 (U.S. EPA 2004). While the bulk of the research is originating in Germany, Japan, the U.K., and

the U.S., 20 other nations are also participating, (OECD 2004).

2.4 Comparison of U.S. and EU HPV Chemical Testing Programs

EPA’s HPV Challenge Program and the EU’s Exis ting Chemical Program involve a similar set

of tests (U.S. EPA 2003c; European Chemicals Bureau 2003; Commission of the European

Communities 2003; Piccirillo 2003). The EU REACH program, however, calls for several tiers

of testing, with more intensive testing required for chemicals produced at relatively high volume

and less intensive testing required for chemicals produced at relatively low volume. Table 2

below provides a comparison between these two programs.6Table 2. Comparison of HPV and REACH Testing ProgramsEU REACH Proposal — Tiered Testing Based on Annual Volume of Chemical Produced or Imported to the EU1 to 10 metric tonnesa10 to 100 metric tonnes100 to 1,000 metric tonnes1,000 metric tonnes or moreEPA HPV“Limited Set”(Described in Annex V)“Base Set”(Described in Annex VI)“Base Set + “Level 1”(Described in Annex VII)“Base Set” + “Level 1” + “Level 2”(Described in Annex VIII)Estimated number of chemical substances being sponsored2,08911,711 + 1,061 intermediatesb3,466b1,645b. It is expected that some ofthese will ultimately be exemptedfrom Level 1 testing.1,799b. It is expected that some of thesewill ultimately be exempted from Level 1or Level 2 testing.Tests performedPhysical-Chemical DataCMelting pointCBoiling pointCDensity (relative density)CVapour pressureCPartition coefficient (noctanol/water)CWater solubilityCpH value and pKa valueCOxidation-reduction potentialCAdsorption/ desorption to soildCMelting-pointCBoiling-pointCRelative densityCVapour pressureCSurface tensionCWater solubilityCPartition coefficient n-octanol/waterCFlash-pointCFlammabilityCExplosive propertiesCSelf-ignition temperatureCOxidizing propertiesCGranulometrySame as in column to the leftTests described in the column tothe left, plus:CStability in organic solventsand identity of relevantdegradation productsCDissociation constantCViscositySame as in column to the leftToxicological StudiesCAcute toxicityCRepeated dose toxicityCDevelopmental toxicity/TeratogenicityCExperiences with human exposureCSkin irritation or skin corrosionCEye irritationCSkin sensitizationCMutagenicity:In vitrogene mutationstudy in bacteriaTests described in the column to the left,plus:CSkin irritation;In vivoskin irritationCEye irritation:In vivoeye irritationCMutagenicity:In vitrocytogenicitystudy in mammalian cells;In vitrogenemutation study in mammalian cellsCAcute toxicity: by oral route; byinhalation; by dermal routeCRepeated dose toxicity: short-termrepeated dose toxicity study (28 days)CReproductive toxicity: screening forreproductive/ developmental toxicity;developmental toxicity studyCToxicokineticsTests described in the column tothe left, plus:CRepeated dose toxicity: shortterm repeated dose toxicitystudy (28 days); sub-chronictoxicity study (90 days)CReproductive toxicity:developmental toxicity study(additional); two-generationreproductive toxicity studyTests described in the column to the left,plus:CReproductive toxicity: two-generationreproductive toxicity study(additional)7Environmental Fate and PathwayscCPhotodegradationCStability in water (hydrolysis)CMonitoring data (environment)CTransport and distribution betweenenvironmental compartmentsincluding estimated environmentalconcentrations and distributionpathwaysCBiodegradationCDegradation: biotic; abioticCFate and behavior in the environment:adsorption/ desorption screening studyCDegradation: biotic(additional);identification of degradationproductsCFate and behavior in theenvironment: adsorption/desorption (additional);bioconcentration in oneaquatic species, preferablyfishCDegradation: biotic(additional)CFate and behavior in the environment(additional)Ecotoxicological StudiesCAcute/prolonged toxicity to fishCAcute toxicity to aquaticinvertebrates (daphnia)CToxicity to aquatic plants e.g. algaeCChronic toxicity to aquaticinvertebrates (daphnia)CToxicity to terrestrial organismsCAvian dietary toxicity testCAvian reproduction testCEarthworms acute toxicity testCTerrestrial plants, growth testCAquatic toxicity: Short-term toxicitytesting onDaphniaTests described in the column to the left,plus:CAquatic toxicity: Growth inhibition studyon algae; Short-term toxicity testing onfish; Activated sludge respirationinhibition testingests described in the column to theleft, plus:CAquatic toxicity: Long-termtoxicity testing onDaphnia;Long-term toxicity testing onfishCEffects on terrestrialorganisms: Short-termtoxicity to earthworms;Effects on soil microorganisms; Short-termtoxicity to plantsTests described in the column to the left,plus:CEffects on terrestrial organisms: Longterm toxicity to earthworms; Longterm toxicity to soil invertebrates;Long-term toxicity to plantsCLong-term toxicity to sedimentorganismsCLong-term or reproductive toxicity tobirdsSources: US. EPA 2003c, Commission of the European Communities 2003, Risk & Policy Analysts 2003.a Also required for isolated intermediates transported in quantities of greather than 1,000 tonnes per yearbSee Risk & Policy Analysts 2003, p. 35 and 37. Figures do not include polymers.cEU documentation lists these tests under the category of “Ecotoxicological Studies”dThis test may also be categorizedunder Environmental Fate and Pathways

# 8 2.5 Impact of the HPV Challenge and REACH on Chemical Testing Demand

Testing demand to satisfy data needs for the HPV Challenge has been lower than initially

expected because many of the data gaps identified in EPA’s HPV testing initiative have been

filled using existing research, thereby avoiding the need for new testing. For example,

Environmental Defense’s “HPV Tracker” tool indicates that, based on test plans filed through

July 2004, no further testing is planned for 460 of 1,338 chemicals (34.4 percent)

(Environmental Defense, 2004).

EPA’s own analysis indicates the amount of new testing required may be even lower. Through

August 2003, EPA had received and reviewed (but not necessarily approved) test plans covering

approximately 790 HPV chemicals. Each test pl an addresses the 15 SIDS endpoints, thus the

test plans reviewed address a total of 11,850 endpoi nts. The reviewed test plans suggest that

approximately 6,800 endpoints, or 45 percent of the total, can be satisfied with existing data (see

Table 3). For another 50 percent, or 7,400 endpoints, data was submitted based on analogy,

structure-activity relationship modeling, technical discussion, “read-across,” or computer and

mathematical modeling. Sponsors plan to conduct actual new testing to fill data gaps for only the

remaining 785 endpoints. This would represent just 6.5 percent of the endpoints required to

fulfill the SIDS testing requirements for these 790 chemicals 2 

# (U.S. EPA 2004b).

2 

# It is important to note that the test plans reviewed represent only 38 percent of all HPV chemicals. For the

remaining chemicals it is not known whet her existing data or modeling results will satisfy the testing requirements

to the same degree.

# 910Table 3. Summary of Test Requirements for 790 Sponsored HPV Chemicalsa,bChemical PropertiesEnvironmental Fate andPathwaysEcotoxicityHealth EffectsTesting Status Tot alsNumber of ChemicalsProposed for testing2538157389960325475768173729477076785Analogy, SAR, Estimation29029937244436558334341463436340545082323584183895014777,345Adequate existing data3253853202423071223611418034429223405323832523301852055,040Testing based on results of othercategory members0041180313444000000042Reproductive and developmentaltesting will depend on results ofrepeat dose studies00000000000000001539Not applicable due tophysical/chemical properties150687929286825200573232347811911612326251,748Not addressed in test plan0001001010000013003441TOTAL79079079079079079079079079079079079079079079079079079079015,010aBased on EPA’s preliminary review of submitted test plans as of August 29, 2003.bThe columns show 19 endpoints, however only15 must be completed to fulfill the SIDSdossier. For example: the transport and distribution test is optional; submitters may complete thegenetic toxicity requirement using eitherin vivoorin vitromethods; and submitters may complete either the repeateddose toxicity test or a combination of the reproductive anddevelopmental toxicity testing. See U.S. EPA (2003c) for further details.